Results: Mean colony counts in antibiotic-free plates (whole pneumococcal population) increased (from 0 to 12 h) from log10 7.0 to 6.3 in drug-free simulations (control), from log10 6.6 to 3.6 in CDN simulations, from log10 6.6 to 8.0 in CXM simulations, from log10 7.0 to 7.2 in CEC simulations, and from log10 6.7 to 7.4 in CFM simulations. At 12 h of control drug-free experiments, the dominant population was Ser4 (70.0%). The small final population after CDN simulations included 48% Ser23F and 20% Ser19F. With all other compounds, the final population was higher than initial inocula, and corresponded to 90% Ser19F after CXM simulations, 61% Ser19F and 35% Ser23F after CEC simulations, and 96% Ser19F after CFM simulations.

Conclusion: Strain distribution in antibiotic-free environment depends on bacterial fitness in mono- and multi-strain niches. The selective pressures of antimicrobial regimens eradicate some populations and unmask minor populations, thus redistributing the whole population. CDN was the only cephalosporin showing bactericidal activity (≥3 log10 reduction of initial inocula) at 12 h of the whole initial population, with a small remaining population mainly composed by Ser23F. All other oral cephalosporins selected populations higher than initial inocula mainly composed by Ser19F.